Patients suffering from manic, depressive, schizoaffective, and anxiety-related disorders are longitudinally evaluated and treated. Double-blind, placebo-controlled clinical trials are employed. Classical neurotransmitters and their metabolites, as well as hormones and peptides that have been implicated in the regulation of mood and behavior, are measured in blood and CSF of patients to assess their relationship to normal and pathological behavior. Alterations in cognitive function, neurophysiology, and biochemistry are explored in relationship to predictors and mechanisms underlying clinical response to anticonvulsants, dopaminergic and noradenergic receptor agonists, the paradoxical therapeutic effects of sleep deprivation in depression, and related treatments of mood and anxiety disorders. Ongoing clinical trials with carbamazepine indicate it may be a useful alternative to lithium carbonate for the acute and prophylactic treatment of manic-depressive illness. Its mechanisms of action in affective illness are being explored. Animal models of electrical kindling and stimulant-induced behavioral sensitization are explored in order to examine mechanisms underlying progressive changes in behavioral pathology.